Sodium Thiosulfate for Chemotherapy-Induced Hearing Loss

Overseen By Site Contact Cincinnati Children's Hospital Medical Center

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's Hospital Medical Center, Cincinnati

Must be taking: Cisplatin, Sodium thiosulfate

Must not be taking: Tacrolimus, Sirolimus

Disqualifiers: Uncontrolled infection, Heart failure, RTA, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether Sodium Thiosulfate can prevent hearing loss in patients undergoing specific cisplatin-based chemotherapy treatments. The study will examine two treatment plans: one using only Cisplatin and Sodium Thiosulfate, and another adding Vorinostat, a medication that may help fight cancer. Individuals previously treated with cisplatin who experienced changes in their cancer's response might be suitable candidates. The trial targets those with tumors such as Wilms tumor, Germ Cell Tumor, or Neuroblastoma. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received myelosuppressive chemotherapy or immunotherapy within 2 weeks before joining the study. If you are on tacrolimus or sirolimus, your levels must be 10 ng/mL or lower.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sodium thiosulfate (STS) is generally safe for people. One study found that adding STS to chemotherapy reduced the risk of hearing loss caused by cisplatin, a common cancer treatment. This finding suggests that STS can protect hearing without causing serious side effects.

Another study found that both adults and children with cancer tolerated STS well when used to prevent hearing damage. These studies did not report any severe side effects from STS; instead, participants experienced fewer problems with hearing loss.

STS has also been tested for safety in different situations, including during pregnancy, without causing harm. This supports the idea that STS is safe for various groups of people.

Overall, while more research is ongoing, current data indicate that STS is usually safe for preventing hearing loss in people receiving cisplatin chemotherapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Sodium thiosulfate is unique because it targets chemotherapy-induced hearing loss by potentially protecting the ears from damage caused by platinum-based chemotherapies like cisplatin. Unlike standard treatments that primarily focus on managing hearing loss after it occurs, sodium thiosulfate may help prevent it from happening in the first place. Researchers are excited about this treatment because it offers a proactive approach, which could significantly improve the quality of life for patients undergoing chemotherapy.

What evidence suggests that Sodium Thiosulfate could be effective in preventing chemotherapy-induced hearing loss?

Research has shown that sodium thiosulfate (STS) can help prevent hearing loss caused by cisplatin, a common chemotherapy drug. This trial will assign participants to different treatment arms to evaluate STS's effectiveness. One study found that adding STS to cisplatin treatment resulted in fewer patients experiencing hearing loss. Another study showed that patients treated with STS did not experience hearing loss, aligning with previous successful studies. Additionally, a specific sodium thiosulfate injection called PEDMARK® demonstrated that only 39% of patients had hearing loss, compared to a higher percentage without it. These findings suggest that STS effectively protects against hearing damage during chemotherapy. ^{3 4 6 7 8}

Who Is on the Research Team?

Katherine Somers, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for patients aged 1 month to 39 years with hepatoblastoma or certain other cancers, who have previously responded to cisplatin but now show progression or resistance. They must have a life expectancy of at least 8 weeks, good organ function, and no severe side effects from previous treatments. Pregnant women and those with heart failure or uncontrolled illnesses are excluded.

Inclusion Criteria

I am not currently in another clinical trial or taking experimental treatments.

My cancer is one of the following types: hepatoblastoma, Wilms tumor, germ cell tumor, or neuroblastoma.

My liver tests are within the required range.

Exclusion Criteria

I have RTA with low bicarbonate and phosphate levels.

I am sexually active and not using birth control.

I do not have any uncontrolled illnesses or infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cisplatin-based therapy with Sodium Thiosulfate (STS) and possibly Vorinostat/SAHA for relapsed/refractory hepatoblastoma and other embryonal tumors

Up to 5 years

Follow-up

Participants are monitored for safety, prevention of hearing loss, and tumor response

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Sodium Thiosulfate

Trial Overview The study tests the effectiveness of Sodium Thiosulfate (STS) in preventing hearing loss when given alongside cisplatin-based chemotherapy. There are two regimens: CS (Cisplatin/STS) for those previously sensitive to cisplatin, and CSS (Cisplatin/STS/Vorinostat) for those who've shown progression on or resistance to cisplatin.

How Is the Trial Designed?

Group I: Stratum 2B- Regimen CSS Experimental Treatment 1 Intervention

Wilms tumor, GCT, Neuroblastoma

Group II: Stratum 2A- Regimen CSS Experimental Treatment 1 Intervention

Cisplatin resistant or progressed on cisplatin after initial response (when given at first diagnosis)

Group III: Stratum 1- Regimen CS Experimental Treatment 1 Intervention

Cisplatin sensitive/no progression on cisplatin (when given at first diagnosis)

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

Trans-tympanic injections of sodium thiosulfate (STS) gel were found to be safe for the middle and inner ears in patients undergoing cisplatin treatment for cancer, with no significant adverse effects reported.

While the average hearing loss was slightly less in treated ears compared to control ears (1.3 dB), the difference was not statistically significant, indicating that further research is needed to enhance the efficacy of STS in preventing cisplatin-induced hearing loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial to test the efficacy of trans-tympanic injections of a sodium thiosulfate gel to prevent cisplatin-induced ototoxicity in patients with head and neck cancer. Rolland, V., Meyer, F., Guitton, MJ., et al.[2022]

Sodium thiosulfate has shown efficacy in protecting hearing in pediatric patients undergoing treatment with cisplatin, although its impact on overall survival varies depending on the disease stage, as seen in the ACCL0431 trial.

Previous systemic drugs like amifostine and disulfiram did not demonstrate hearing preservation, highlighting the need for future studies to focus on better-designed trials with larger sample sizes and standardized ototoxicity endpoints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions for cisplatin-induced hearing loss in children and adolescents with cancer. Freyer, DR., Brock, P., Knight, K., et al.[2023]

Sodium thiosulfate (STS) effectively reduces carboplatin-induced hearing loss in guinea pigs, suggesting it could protect against ototoxicity when carboplatin is used to treat brain tumors with osmotic blood-brain barrier disruption.

Timing of STS administration is crucial; it must be given within 8 hours after carboplatin to be effective, and it is neurotoxic if given immediately after blood-brain barrier disruption, but safe if given 60 minutes later when the barrier is reestablished.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and animal studies of sodium thiosulfate as a potential chemoprotectant against carboplatin-induced ototoxicity. Neuwelt, EA., Brummett, RE., Remsen, LG., et al.[2015]

In a phase 3 trial involving 125 children and adolescents undergoing cisplatin chemotherapy, sodium thiosulfate significantly reduced the incidence of hearing loss, with only 28.6% of participants in the sodium thiosulfate group experiencing hearing loss compared to 56.4% in the control group.

Sodium thiosulfate was found to be safe, with no serious adverse events attributed to its use, suggesting it could be a valuable protective treatment against cisplatin-induced hearing loss in pediatric cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431): a multicentre, randomised, controlled, open-label, phase 3 trial. Freyer, DR., Chen, L., Krailo, MD., et al.[2022]

Sodium thiosulfate (Pedmark®) has been approved in the USA as a chemoprotectant to reduce the risk of hearing loss in pediatric patients receiving cisplatin chemotherapy, specifically for those aged 1 month and older with localized, non-metastatic solid tumors.

The mechanism of action involves sodium thiosulfate interacting with cisplatin to form inactive compounds and enhancing cellular antioxidant defenses, which helps prevent ototoxicity associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium Thiosulfate: Pediatric First Approval. Dhillon, S.[2023]

Sodium thiosulfate (STS) significantly reduces the risk of ototoxic effects in patients undergoing platinum-based chemotherapy, with a relative risk of 0.61, based on a meta-analysis of 4 studies involving 278 patients.

The use of STS did not lead to a significant increase in the risk of poor event-free survival or overall survival, suggesting it can be safely used to protect against hearing loss without compromising cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Sodium Thiosulfate With Risk of Ototoxic Effects From Platinum-Based Chemotherapy: A Systematic Review and Meta-analysis. Chen, CH., Huang, CY., Lin, HH., et al.[2022]

In a study involving 29 patients with malignant brain tumors, sodium thiosulfate (STS) significantly reduced the incidence of carboplatin-induced ototoxicity, with only 3.7 dB hearing loss in the STS group compared to 20.8 dB in a historical control group (79% incidence of ototoxicity).

Doses of 16 or 20 g/m2 of STS were effective in protecting hearing without affecting the central nervous system, marking a novel approach to prevent drug-induced hearing loss while maintaining the efficacy of carboplatin treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First evidence of otoprotection against carboplatin-induced hearing loss with a two-compartment system in patients with central nervous system malignancy using sodium thiosulfate. Neuwelt, EA., Brummett, RE., Doolittle, ND., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8329743/

Association of Sodium Thiosulfate With Risk of Ototoxic ... This systematic review and meta-analysis investigates 4 studies for the association of sodium thiosulfate with reduced risk of ototoxic ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1801109

Sodium Thiosulfate for Protection from Cisplatin-Induced ... The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e15075

Effect of sodium thiosulfate anhydrous on cisplatin-induced ... No hearing loss was observed/ detected post-treatment and the tumor outcomes were consistent with the Phase 3 studies. This is very encouraging.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9635495/

Sodium thiosulfate for prevention of cisplatin-induced ... A large proportion of patients results in cisplatin-induced hearing loss, a debilitating and permanent late effect, with consequences for neurocognition.

5. ncoda.org ncoda.org/wp-content/uploads/2025/10/NCODA-Poster-Presentation_2025_JLong.pdf

PEDMARK® (sodium thiosulfate injection) Prevents ... Results confirmed PEDMARK's efficacy in reducing cisplatin-induced hearing loss: • 39% of patients experienced hearing loss in the. PEDMARK arm compared to ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/212937s000lbl.pdf

212937s000lbl.pdf - accessdata.fda.gov Oral or intravenous administration of sodium thiosulfate during the period of organogenesis resulted in no signs of malformations or lethality, but at doses and ...

7. ec.europa.eu ec.europa.eu/health/documents/community-register/2024/20240606162780/anx_162780_en.pdf

Pedmarqsi, INN-sodium thiosulfate Study 2 – supportive study. Study 2 was a multicentre, randomised, controlled, open-label study to assess the efficacy and safety of STS in preventing hearing ...

8. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.02353

Use of Sodium Thiosulfate as an Otoprotectant in Patients ... Overall, systemic STS effectively reduces CIHL in the preclinical and controlled clinical study settings, in both adults and children with cancer.